Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation

Koichi Matsuo, Jane M. Owens, Martin Tonko, Candace Elliott, Timothy J. Chambers, Erwin F. Wagner

Research output: Contribution to journalArticle

240 Citations (Scopus)

Abstract

Osteoclasts are bone-resorbing cells derived from haematopoietic precursors of the monocyte-macrophage lineage. Mice lacking Fos (encoding c- Fos) develop osteopetrosis due to an early differentiation block in the osteoclast lineage. c-Fos is a component of the dimeric transcription factor activator protein-1 (Ap-1), which is composed mainly of Fos (c-Fos, FosB, Fra-1 and Fra-2) and Jun proteins (c-Jun, JunB and JunD). Unlike Fra-1 (encoded by Fos/1), c-Fos contains transactivation domains required for oncogenesis and cellular transformation. The mechanism by which c-Fos exerts its specific function in osteoclast differentiation is not understood. Here we show by retroviral-gene transfer that all four Fos proteins, but not the Jun proteins, rescue the differentiation block in vitro. Structure-function analysis demonstrated that the major carboxy-terminal transactivation domains of c-Fos and FosB are dispensable and that Fra-1 (which lacks transactivation domains) has the highest rescue activity. Moreover, a transgene expressing Fra-1 rescues the osteopetrosis of c-Fos-mutant mice in vivo. The osteoclast differentiation factor Rankl (also known as TRANCE, ODF and OPGL; refs 8-11) induces transcription of Fos/1 in a c-Fos-dependent manner, thereby establishing a link between Rank signalling and the expression of Ap-1 proteins in osteoclast differentiation.

Original languageEnglish
Pages (from-to)184-187
Number of pages4
JournalNature Genetics
Volume24
Issue number2
DOIs
Publication statusPublished - 2000 Feb
Externally publishedYes

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Osteoclasts
Proto-Oncogene Proteins c-jun
Transcriptional Activation
Osteopetrosis
Transcription Factor AP-1
RANK Ligand
Proteins
Transgenes
Monocytes
Carcinogenesis
Transcription Factors
Macrophages
Bone and Bones
Genes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Matsuo, K., Owens, J. M., Tonko, M., Elliott, C., Chambers, T. J., & Wagner, E. F. (2000). Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation. Nature Genetics, 24(2), 184-187. https://doi.org/10.1038/72855

Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation. / Matsuo, Koichi; Owens, Jane M.; Tonko, Martin; Elliott, Candace; Chambers, Timothy J.; Wagner, Erwin F.

In: Nature Genetics, Vol. 24, No. 2, 02.2000, p. 184-187.

Research output: Contribution to journalArticle

Matsuo, K, Owens, JM, Tonko, M, Elliott, C, Chambers, TJ & Wagner, EF 2000, 'Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation', Nature Genetics, vol. 24, no. 2, pp. 184-187. https://doi.org/10.1038/72855
Matsuo, Koichi ; Owens, Jane M. ; Tonko, Martin ; Elliott, Candace ; Chambers, Timothy J. ; Wagner, Erwin F. / Fos/1 is a transcriptional target of c-Fos during osteoclast differentiation. In: Nature Genetics. 2000 ; Vol. 24, No. 2. pp. 184-187.
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